O-231 - LONG-TERM RESULTS OF AUTOLOGOUS MICRO-FRAGMENTED ADIPOSE TISSUE FOR DIABETIC FOOT MINOR AMPUTATIONS IN A RANDOMIZED CONTROLLED SINGLE-CENTER CLINICAL TRIAL (MIFRAADIF)

TOPIC:
Wound healing
AUTHORS:
Nicola L. (Department of Vascular Surgery, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia ~ Modena ~ Italy) , Federica G. (Department of Vascular Surgery, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia ~ Modena ~ Italy) , Stefano G. (Department of Vascular Surgery, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia ~ Modena ~ Italy) , Roberto S. (Department of Vascular Surgery, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia ~ Modena ~ Italy)
Introduction:
Diabetic foot ulcer (DFU) is a common complication of diabetes mellitus.1 The injection of micro-fragmented autologous adipose tissue at the minor amputation stump for DFU (MiFrAADiF trial) demonstrated a better healing rate along with quality of life and length of hospital improvements.2,3 The MiFrAADiF technique was introduced recently within minor amputations, and long-term safety and clinical data are still warranted.
Methods:
A total of 114 patients were enrolled and individually randomized in a two-arm, controlled single-center clinical trial. The trial was registered in ClinicalTrials.gov (NCT03276312). Fifty-seven patients were allocated to local injection of autologous micro-fragmented adipose tissue at the amputation wound (treatment group) and 57 to standard clinical care (control group). Forty-four and twenty-three patients being part of the treatment and the control group respectively healed at 6 months (previously published).3 This report aimed for the results of healed patients beyond 6 months up to February 28th, 2022. The primary object was long-term safety defined as the absence of either adverse events or mortality likely related to the adipose injection. Causes of death and adverse events were distinguished as being technique-related or not. The secondary endpoints were the occurrence of trophic lesions, reamputation, revascularization, and survival. The trophic lesions were categorized as relapse or new lesions if they involved the stump or not. The reamputation defined the need for an amputation that included the index stump. Minor amputations were those up to the forefoot. Revascularizations were additional interventions to improve the arterial patency. Survival was the time between the index procedure and death or the follow-up end. Count and percentage reported for categorical and mean ± standard deviation for continuous variables. Between-groups comparisons were performed with chi2-test and t-test, categorical and continuous respectively. Kaplan-Meier analysis estimated time-dependent endpoints.
Results:
All results were reported for the treatment vs control group. Mean follow-up was 54.5±20.6 vs 44.2±23.9 months (P=0.070). The long-term safety was confirmed by the absence of either adverse events and deaths related to the injection of adipose tissue. Ten (22.7%) vs 6 (26.1%) patients experienced the occurrence of trophic lesions (P=0.683). It was a relapse in 3 patients for both group (6.8 vs 13.0%; P=0.397) with the remaining being new trophic lesions. The relapse mean time was 19.5±12.6 months. All the relapse patients received reamputation with 1 being major within each group. Relapses were complicated by an infection determining sepsis in 3 patients. The freedom from relapses for the treatment group was 95.4%, 92.8%, and 92.8% at 12, 36, and 60 months respectively (Figure 2). The estimated values for the control group were 89.5%, 82.0%, and 82.0% at 12, 36, and 60 months respectively. Revascularization was indicated in 6 (13.6%) and 3 (13.0%; P=0.946). The revascularization was an open bypass in 3 (50.0%) and 2 (66.7%). It was endovascular in 3 (50.0%) and 1 (33.3%; P=0.893). Survival for the treatment group was 88.6%, 75.0%, and 48.5% at 12, 36, and 60 months respectively (Figure 2). Survival estimated values for the control group were 65.2%, 52.2%, and 42.2% at 12, 36, and 60 months respectively.
Conclusion:
The MiFrAADiF trial demonstrated the long-term safety of micro-fragmented autologous adipose tissue injection in minor amputations for DFU. Relapses, reamputations, revascularizations, and survival did not differ significantly between groups. The hypothesis is that the autologous adipose tissue exerts its role in the healing period of the amputation's wound. However, larger studies should confirm this assumption. Meanwhile, the MiFrAADiF is a valid and safe technique to improve outcomes of diabetic foot ulceration undergoing minor amputation.
References:
1. Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis †. Ann Med. 2017;49:106-16. 2. Lonardi R, Leone N, Gennai S, Trevisi Borsari G, Covic T, Silingardi R. Autologous micro-fragmented adipose tissue for the treatment of diabetic foot minor amputations: a randomized controlled single-center clinical trial (MiFrAADiF). Stem Cell Res Ther. 2019;10:223. 3. Gennai S, Leone N, Covic T, Migliari M, Lonardi R, Silingardi R. Health-related quality of life outcomes and hospitalization length of stay after micro-fragmented autologous adipose tissue injection in minor amputations for diabetic foot ulceration (MiFrAADiF Trial): results from a randomized controlled single-center clinical trial. Int Angiol. 2021;40:512-9.
ATTACHMENTS: